Diseases in Biochemistry Flashcards
Mitochondrial disease characterized by bilateral loss of central vision due to neuroretinal degeneration. This is characterized by deficiency in which complex of the ETC?
Leber’s Hereditary Optic Neuropathy
Complex III
Inherited condition due to NADH:Q oxidoreductase (Complex I) deficiency. It is caused by a mutation in mitochondrial DNA and may be involved in Alzheimer’s disease and DM.
MELAS
Mitochondrial encephalopathy, lactic acidodis and stroke
Prion diseases are characterized by alteration of the conformation and physical properties of proteins endogenous to the human host. Normal PrP is a glycoprotein rich in ___ (secondary structure) while PrPsc has many ____.
PrP: alpha helices
PrPsc: beta sheets
Most fatal of the mitochondrial diseases characterized by deficiency in all complexes of the ETC
Fatal infantile mitochondrial myopathy
Mitochondrial disease characterized by deficiency in Complex II
Kearns-Sayre Syndrome
Mitochondrial disease characterized by deficiency in Complex IV
Leigh’s Disease
Manifests as chronic hemolytic anemia, this condition is the most common enzyme defect in glycolysis.
Pyruvate kinase deficiency.
Aldolase A is another glycolytic enzyme that may be deficient.
The exercise capacity of patients with ___ is low particularly if they are on high carbohydrate diets. By providing lipid as an alternative fuel (during starvation), when blood free fatty acid and ketone bodies are increased, work capacity is impoved.
Muscle phosphofructokinase deficiency
Most common biochemical cause of congenital lactic acidosis. What is the pattern of inheritance?
Pyruvate dehydrogenase deficiency.
Because enzyme is deficient, pyruvate is shunted towards lactate production. Patients present with lactic acidosis and neurologic disturbance.
X-linked dominant!
There are only a few diseases that are X-linked dominant; another example is Alport Syndrome.
Glycogen accumulation in liver and renal tubule cells; hypoglycemia; lactic acidemia; ketosis; hyperlipemia
Most likely diagnosis? Deficient enzyme?
Von Gierke’s Disease (Type I)
Glucose-6-phosphatase
Accumulation of glycogen in lysosomes.
Juvenile form: muscle hypotonia, death from heart failure by2.
Adult form: muscle dystrophy
Pompe’s Disease (Type II)
Lysosomal a1>4, a1>6 glucosidase
(Acid maltase)
MNEMONIC: Pompe’s affects the pump (heart).
Fasting hypoglycemia; hepatomegaly in infancy; accumulation of characteristic branched polysaccharide
Cori’s (or Forbe’s) Disease (Type III)
Debranching enzyme
MNEMONIC: ABCD
Andersen’s = Branching enzyme
Cori’s = Debranching enzyme
Hepatosplenomegaly; accumulation of polysaccharide with few branch points. Death from heart or liver failure in first years of life
Andersen’s (Amylopectinosis) (Type IV)
Branching enzyme
MNEMONIC: ABCD
Andersen’s = Branching enzyme
Cori’s = Debranching enzyme
Poor exercise tolerance. Muscle glycogen abnormally high. Blood lactate very low after exercise.
McArdle’s syndrome (Type V)
Muscle phosphorylase
McArdle's = Muscle phosphorylase HEr's = HEpatic phosphorylase
Hepatomegaly; accumulation of glycogen in liver; mild hypoglycemia; generally good prognosis
Her’s Disease (Type VI)
Liver phosphorylase
McArdle's = Muscle phosphorylase HEr's = HEpatic phosphorylase
Poor exercise tolerance. Muscle glycogen abnormally high. Blood lactate very low after exercise. AND HEMOLYTIC ANEMIA
Tarui’s Disease
Muscle and erythrocyte phosphofructokinase I
Hepatomegaly; accumulation of glycogen in liver; mild hypoglycemia; generally good prognosis
Her’s Disease (Type VI)
Liver phosphorylase
In the rare hereditary condition, considerable quantities of L-xylulose appear in the urine because of the absence of the enzyme necessary to reduce L-xylulose to xylitol.
Essential pentosuria.
Aminopyrine and antipyrine increase the excretion of L-xylulose.
Benign and asymptomatic condition whose only symptom is the appearance of fructose in blood and urine. What is the enzyme deficiency?
Essential fructosuria;
hepatic fructokinase
Characterized by lack of hepatic fructokinase
Essential fructosuria
Characterized by lack of aldolase B. Causes fructose-induced hypoglycemia because high levels of fructose-1-phosphate allosterically inhibit liver phosphorylase
Hereditary fructose intolerance
Autosomal recessive condition in which galactitol accumulates causing cataracts within a few days of birth; vomiting and diarrhea after milk ingestion; hepatosplenomegaly; and mental retardation. This condition is due to deficiency in ___.
Classic galactosemia
Galatose-1-phosphate uridyltransferase
A benign condition characterized by galactosemia, galactosuria and an increased tendency for cataracts
Galactokinase deficiency
This condition is characterized by low levels of docosahexaenoic acid
Retinitis pigmentosa
Inherited defect in fatty acid metabolism; affects only the liver; results in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.
CPT-I deficiency
Inherited defect in fatty acid metabolism; affects mainly the skeletal muscle; results in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.
CPT-II deficiency
Hypoglycemia occurs after eating the unripe fruit of the akee tree, which contains hypoglycin - an inactivator of medium and short chain acyl-CoA dehydrogenase
Jamaican vomiting sickness
Characterized by excretion of C6 - C10 dicarboxylic acids and by nonketotic hypoglycemia. What is the deficient enzyme?
Dicarboxylic aciduria
Medium chain acyl-CoA dehydrogenase
Neurologic disorder due to metabolic defect resulting in accumulation of phytanic acid found in dairy products and ruminant fat and meat.
Refsum’s disease
Rare inherited absence of peroxisomes in all tissues. They accumulate C26 - C38 polyenoic acids in brain tissue; causing severe neurologic deficits.
Zellweger’s syndrome
Deficiency in medium chain fatty-acyl dehydrogenase leads to fasting hypoglycemia. Pediatric patients are susceptible to this condition.
Sudden infant death syndrome
Most common leukodystrophy. This is characterized by deficiency in which enzyme.
Symptoms include mental retardation, psychologic disturbances in adults. Demyelination.
Metachromatic leukodystrophy
Arylsulfatase A
MNEMONIC:
This condition is characterized by psychologic disturbances.
METAchromatic = ME TAMA sa ulo!
Name all glycogen storage disorders from Type I to Type VI
Viagra Pills Cause A Major Hard-on
I: Von Gierke II: Pompe III: Cori IV: Andersen V: McArdle's VI: Her's
Name all lysosomal storage disorders from Type I to Type VI
Viagra Pills Cause A Major Hard-on
I: Von Gierke II: Pompe III: Cori IV: Andersen V: McArdle's VI: Her's
X-linked recessive disorder. Clinical symptoms include skin rash, kidney failure. Full symptoms are seen only in males.
Fabry’s disease.
MNEMONIC: FFAABBBRY Foam cells found in glomeruli and tubules Febrile episodes Alpha galactosidase A deficiency Angiokeratomas Burning pain in extremities BUN increased in serum Boys Renal failure YX genotype (male, X linked recessive)
Also ZeBRa bodies
Mutation in sickle cell anemia
“HbS isn’t Very Good”
At sixth position of Hb beta chain, Valine is present instead of Glutamic acid.
SICKle cell = SIXth amino acid of Hb b chain
Triad of skin rash, hoarseness, bone malformation. WHat is the deficient enzyme?
Farber’s Disease
Ceramidase
Characterized by hepatosplenomegaly, erosion of long bones, mental retardation in infants.
Gaucher’s Disease
Deficiency in b-glucosidase
Characterized by hepatosplenomegaly, erosion of long bones, mental retardation in infants.
Gaucher’s Disease
Characterized by mental retardation; myelin almost absent. Peripheral neuropathy, optic atrophy
Krabbe’s disease
Deficiency in b-galactosidase
“The Crab Nebula is a GALaxy”
Deficiency in galactocerebrosidase;
Has GLOBOID cells
This disease is caused by a deficiency in:
- b-glucosidase
- b-galactosidase
- Gaucher’s
- Krabbe’s
GaUchers: b-glUcosidase
KrAbbe’s: b-gAlactosidase
This condition is characterized by hepatosplenomegaly, mental retardation and is fatal in early life.
Niemann-Pick
Sphingomyelinase
MNEMONIC:
Niemann Picks his nose with his sFINGERS (sphingomyelinase).
Which sphingolipidoses are characterized by the presence of a cherry-red macula?
Tay-Sach’s
Niemann-Pick’s
In multiple sclerosis, there is loss both phospholipids and sphingolipids in the white matter. Which phospholipid in particular is lost in MS?
Ethanolamine plasmalogen
A deficiency in LDL receptor causes increased levels of LDL in the peripheral icrculation and an increased risk of atherosclerosis.
Familial hypercholesterolemia
Type II
Familial condition characterized by high VLDL and chylomicron, and low LDL and HDL. Patients are at increased risk for xanthomas and pancreatitis but with no increased risk for coronary atherosclerosis.
Familial lipoprotein lipase deficiency
Type I
Familial condition characterized by high levels of VLDL and chylomicron remnants. Patients are at an increased risk for coronary heart disease. Which is deficient in this condition?
Familial dysbetalipoproteinemia
(Type III)
Deficient ApoE
Familial condition characterized by increased VLDL production. Triad of CAD, DM type 2 and obesity
Familial hypertriglyceridemia
Type IV
Condition is characterized by intestinal malabsorption with accumulation of lipids in intestine and liver. No chylomicron and VLDL found in blood stream.
Abetalipoproteinemia
Deficient apo B
Characterized by deficiency in ABCA (ATP-binding casette transporter 1). Hallmark is hypertrophied orange tonsils
Tangier’s disease
MNEMONIC: Tangier’s = tangerine tonsils
Characterized by deficiency in LCAT.
Causes corneal opacification with hepatosplenomegaly.
Fish eye disease
Condition characterized by high HDL levels, associated with benefits to health and longevity
Familial hyperalphalipoproteinemia
Condition characterized by decreased level or alteration in the structure of cardiolipin. Mitochondrial dysfunction causing heart failure and hypothyroidism
Barth syndrome
In Alzheimer’s Disease, this protein undergoes a conformational transformation from being rich in alpha helices to a state rich in beta sheets. The latter is prone to self-aggregation. Which apolipoprotein has been implicated as a potential mediator of this transformation?
B-amyloid
Apolipoprotein E
Patient presents with cyanosis, anxiety, headache and dyspnea. On extraction, blood was noted to be muddy brown in color. Diagnosis? Immediate treatment?
Methemoglobinemia
(Fe3+ in heme which does not bind O2 but binds CN-)
Mild: oral methylene blue or ascorbic acid
Severe: IV methylene blue
Blood becomes “cherry pink” in color. Due to poisoning with an odorless gas; commonly seen in burn patients. Treatment?
Carbon monoxide poisoning
CO has 200x greater affinity.
Tx: Give 100% O2
An intrinsic defect in RBC membrane that renders erythrocytes less deformable and vulnerable to splenic sequestration. Defect in which protein? Diagnostic test?
Hereditary spherocytosis.
Spectrin
Osmotic fragility test
Patients homozygous for the trait present with mild hemolytic anemia. Hemoglobin variant has lysine at the 6th position instead of glutamate.
Hemoglobin C disease
Anemia, accumulation of Hb Barts. Patients present only after 8 months of life.
Beta thalassemia
Condition characterized by hyperextensible skin, tendency to bleed, hypermobile joints and increased risk of berry aneurysm.
Ehlers-Danlos syndrome
Collagen III
Characterized by multiple fractures, blue sclerae, hearing loss and dental imperfections
Osteogenesis imperfecta
Collagen I
Presents with glomerulonephritis (hematuria), end-stage renal disease, and hearing deficits
Alport’s syndrome
Collagen IV
In this condition, skin easily breaks and blisters as a result of minor trauma. Conditon is due to mutations affecting ___.
Epidermolysis bullosa
(Collagen VII)
Collagen VII forms delicate fibrils that anchor basal lamina to collagen fibrils in the dermis.
Patient all and thin, with dolichostenomelia, arachnodactyly, ascending aortic dilatation and dissection.
Marfan Syndrome
Fibrillin
Genetic cause of emphysema
A1-antitrypsin deficiency
Inhibits elastase
Impairment in human selenoprotein have been implicated in tumorigenesis and atherosclerosis; and are associated with this selenium deficiency cardiomyopathy
Keshan Disease
Condition presents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma and death. May be treated with low protein diet
Hereditary hyperammonemia
Type I: carbamoyl phosphate synthetase I
Type II: ornithine transcarbamoylase
In Type II, mothers also exhibit hyperammonemia and an aversion to high CHON diet.
Patient presents with hyperornithinemia, hyperammonemia, and homocitrullinuria. What is the underlying genetic defect?
HHH Syndrome
Due to defect in ornithine transporter (transports ornithine from cytosol to mitochondria)
Homocitrullinuria develops because transcarbamoylase (in the absence of ornithine), works with lysine to form homocitrulline.
Friable, tufted hair (trichorrhexis nodosa) associated with elevated levels of arginosuccinate in CSF, blood and urine. What is the deficient enzyme? Diagnostic test?
Arginosuccinase deficiency.
Measurement of erythrocyte arginosuccinase activity on umbilical cord blood
1 - 2 g of citrulline daily is excreted in this disorder of urea metabolism.
Arginosuccinate synthetase deficiency
An autosomal recessive condition characterized by hyperargininemia. This condition does not present until patient has reached age 2 to 4 years.
Arginase deficiency
Due to a deficiency in alpha-ketoacid decarboxylase. Causes severe CNS defects, mental retardation and death. Causes increased alpha keto acids in the blood, esp leucine
Maple syrup urine disease
Condition characterized by urolithiasis, nephrocalcinosis and early mortality from renal failure or hypertension. If this was due to a defect in amino acid catabolism, what is the condition and which amino acid is involved?
Primary hyperoxaluria
Defect is failure to catabolize glyoxylate which is oxidized to oxalate (increases stone formation).
Glyoxylate is a product of deamination of GLYCINE.
Increased tendency to form stones due to defective reabsorption of a group of amino acids. What is the treatment?
Cystinuria
No transporter for COAL
Cystine, Ornithine, Arginine, Lysine
Treat with acetazolamide to alkalinize the urine!
Deficiency in tyrosine aminotransferase leads to tyrosinemia
Richner-Hanhart Syndrome
Type II tyrosinemia
In this condition, the urine darkens on exposure to air. Later in the natural history of the disease, there is arthritis and connective tissue pigmentation. What is the condition? Enzyme defect? Pathophysiology of symptoms?
Alkaptonuria due to deficiency in homogentisate oxidase.
Homogentisate is a product of tyrosine catabolism. Oxidation of homogentisate in the urine leads to darkening. Oxidation of homogentisate to benzoquinone acetate poiymerizes and binds to connective tissue, leading to arthritis and pigmentation (ochronosis).
Pellagra like signs and symptoms are seen due to impaired intestinal and renal transport of an amino acid.
Hartnup Disease
Due to impaired transport of Tryptophan and neutral amino acids.
Remember that Tryptophan is required for niacin synthesis
Condition characterized by mental retardation, growth retardation, fair skin, eczema and musty body odor
Phenylketonuria
Due to deficiency in Phenylalanine Hydroxylase
PHenylketonuria = Phenylalanine Hydroxylase
Lack of melanin increases the risk of skin Ca. This condition can result from a lack of migration of neural crest cells.
Albinism
Deficiency in Tyrosinase
This condition can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis.
Homocystinuria due to:
- Cystathionine synthase deficiency (with B6, converts homocysteine to cystathionine and then cysteine).
- Low affinity for cystathionine synthase
- Homocysteine methyltransferase deficiency
(Converts homocysteine to methionine)
Porphyria which presents as decreased red cell counts and hemoglobin
X-linked sideroblastic anemia
ALA synthase deficiency
Photosensitivity or chronic inflammation to overt blistering and shearing in sun-exposed areas; abdominal pain and neuropsychiatric symptoms.
The most common form is due to which enzyme deficiency.
Porphyria cutanea tarda
Deficiency in uroporphyrinogen decarboxylase
Presents with abdominal pain and neuropsychiatric symptoms. Urinary delta-aminolevulinic acid is elevated.
ALA dehydratase deficiency
Most porphyrias are autosomal dominant except ____ which is characterized by deficiency in ___. Does NOT exhibit photosensitivity.
Congenital erythropoietic purpura
(Autosomal recessive)
Uroporphyrinogen III synthase
Presents with headache, memory loss, peripheral neuropathy, nausea, abdominal pain, diarrhea. CBC demonstrates coarse, basophilic stippling of RBC
Lead poisoning
Most common cause of unconjugated hyperbilirubinemia
Neonatal (physiologic) jaundice
Rare autosomal recessive disorder characterized by severe congenital jaundice. Mutations in the gene encoding bilirubin-UGT is characteristic. Disease is often fatal within the first 15 months.
Type I Criggler-Najjar
Type 2 is less severe; and can respond to large doses of Pb
Unconjugated hyperbilirubinemia more common in males and entirely harmless
Gilbert Syndrome
Benign autosomal recessive disorder consisting of conjugated hyperbilirubinemia. Centrilobular hepatocytes contain an abnormal black pigment derived from epinephrine.
Dubin-Johnson Syndrome
Mutation in MRP-2
Rare benign conjugated hyperbilirubinemia. Liver histology is normal. Precise cause unknown
Rotor Syndrome
Severe burning and aching of the feet, hyperesthesia, and vasomotor changes of the feet that leads to excessive sweating
Burning feet syndrome aka
Grierson-Gopalan syndrome
Megaloblastic anemia with degeneration of the spinal cord
Pernicious anemia (Vitamin B12 deficiency)
Clinical manifestations include headache, nauseam ataxia related to increased CSF; hepatomegaly; thickening of long bones and hypercalcemia; and excessive dryness and desquamation of the skin.
Vitamin A toxicity
Most important preventable cause of blindness
Vitamin A deficiency
Cheilosis, desquamation, inflammation of the tongue and a seborrheic dermatitis
Riboflavin deficiency
Photosensitive dermatitis, dementia, diarrhea
Pellagra
B3/niacin deficiency
Triad of hyperuricemia, mental retardation and self-mutilation. Which two metabolites accumulate in this condition?
Lesch-Nyhan Syndrome
HGPRT deficiency
Lesch Nyhan = He’s Got Purine Recovery Trouble
PRPP and uric acid
How does Von Gierke’s syndrome cause hyperuricemia?
Von Gierke’s syndrome is characterized by deficiency in glucose-6-phosphatase which turns G6P (obtained from glycogenolysis) into free glucose. In this syndrome, accumulation of G6P leads to shunting of some G6P into the pentose phosphate pathway, increasing ribose-5-phosphate, and subsequent purine metabolism. Elevated purines eventually are catabolized into uric acid.
Immunodeficiency in which both T cell and B cells are sparse and dysfunctional.
Adenosine deaminase deficiency
ADA converts adenosine to inosine. With deficiency, adenosine builds up, converted to AMP and dATP which inhibits ribonucleotide reductase.
Severe liver damage leads to hypouricemia and increased excretion of hypoxanthine and xanthine. Patients are at an increased risk of xanthine lithiasis.
Xanthine oxidase deficiency
Abnormal growth, megaloblastic anemia and excretion of large amounts of orotate in urine
Orotic aciduria
Due to low activities:
A. Orotidine phosphate decarboxylase
B. Orotate phosphoribosyltransferase
Match condition with characteristic defect in DNA repair.
- Xeroderma pigmentosum
- Hereditary nonpolyposis Ca
A. Mismatch repair
B. Base excision repair
C. Nucleotide excision repair
D. Double-strand break repair
- C
2. A
Marked sensititivity to sunlight and subsequent formation of multiple skin Ca and premature death
Xeroderma pigmentosum
Autosomal recessive
Defect in nucleotide excision repair
Autosomal recessive disorder resulting in development of cerebellar ataxia and lymphoreticular neoplasms. Defect in?
Ataxia telangiectasia
ATM (ataxia telangiectasia mutated) and ATR proteins normally sense DNA damage and phosphorylate (and activate) p53
A congenital disorder of glycosylation. Absence of Golgi-located GDP-fucose transporter leads to absence of fucosylated ligands for selectins. Patients prone to life-threatening, recurrent bacterial infections and psychomotor and mental retardation. What is the tx?
Leukoacyte adhesion deficiency (II)
Tx: oral fucose
Acquired mild anemia characterized by the presence of Hg in urine due to hemolysis of red cells, particularly during sleep. The basic defect in this condition is somatic mutation in this gene. Which 2 proteins are deficient?
Paroxysmal nocturnal hemoglobinuria PIG-A (Phosphatidylinositol glycan class A)
Proteins anchored by GPI missing:
Decay accelerating factor
CD59
In PNH, what 2 proteins are missing? What is their normal function?
Decay accelerating factor
CD59
Interact with components of the complement system to prevent hemolytic action.
At night, drop in pH increases susceptibility to lysis by the complement system.
These conditions are a result of defects in synthesis of glycans in alpha-dystroglycan, which results in defective interaction with laminin-2 (merosin) in basement membrane.
Congenital muscular dystrophies
Walker-Warburg; Muscle-eye-brain disease, Fukuyama
This uncommon disease presents with progressive psychomotor retardation and a variety of physical signs. It is characterized by mutant GlcNAc phosphotransferases. Lack of GlcNAc 1-phosphate on mannose residues on many enzymes lead to secretion of these enzymes rather than being targeted to lysosomes.
I-Cell Disease
Developmental disorder affecting connective tissue and CNS. Increased risk of supravalvular aortic stenosis.
Williams syndrome
Absence of elastin
Characterized by increased bone density and in one form, RTA and cerebral calcification. Enzyme deficiency?
Osteopetrosis
Carbonic anhydrase II
in Chromosome 8 (HARD BONE = 8 letters)
Osteoclasts secrete H+ into environment to increase solubility of hydroxyapatite. Within the cell, OH left is neutralized by H+ formed by normal carbonic anhydrase. In deficiency, osteoclast function is impaired.
Short limbs, normal trunk size, macrocephaly and skeletal abnormalities. Pattern of inheritance? Mutations in gene encoding ___?
AchonDroplasia
Autosomal Dominant
Fibroblast growth factor receptor 3 (FGFR3)
(A tyrosine kinase receptor)
Mutation involved substitution of Arg for Gly
Mutation in genes leading to formation of abnormal Type II collagen, manifests as degeneration of joint cartilage and vitreous body of the eye.
Stickler Syndrome
